Biomedical subjects
Publications and source records attributed to H L Chen.
To investigate the controlled release effect of a thermo-sensitive gel, Pluronic F127 (PF127) on microspheres, poly[D,L-lactic-co-glycolic acid] (PLGA) microspheres were coated with Pluronic F127 gel and the in vitro release was evaluated. The results demonstrated that PF127, which gelled at 37 degrees C, inhibited the initial burst release of drug from microspheres effectively.
An abandoned pentachlorophenol plant and nearby area in southern Taiwan was heavily contaminated by dioxins, impurities formed in the PCP production process. The investigation showed that the average serum PCDD/Fs of residents living nearby area (62.5 pg WHO-TEQ/g lipid) was higher than those living in the non-polluted area (22.5 and 18.2 pg WHO-TEQ/g lipid) (P<0.05). In biota samples, average PCDD/F of milkfish in sea reservoir (28.3 pg WHO-TEQ/g) was higher than those in the nearby fish farm (0.15 pg WHO-TEQ/g), and Tilapia and shrimp showed the similar trend. The average daily PCDD/Fs intake of 38% participants was higher than 4 pg WHO-TEQ/kg/day suggested by the world health organization. Serum PCDD/F was positively associated with average daily intake (ADI) after adjustment for age, sex, BMI, and smoking status. In addition, a prospective cohort study is suggested to determine the long-term health effects on the people living near factory.
After the transfection of alpha-1,3-fucosyltransferase (FucT)-VII cDNA into H7721 human hepatocarcinoma cells, the protein expression of some cyclins, cyclin-dependent kinases (CDKs) and cyclin-dependent kinase inhibitors (CDIs) p16INK4 and p21waf1/Cip1 were unchanged. However, CDI p27Kip1 protein, both the total amount and the amount that bound to CDK2, but not its mRNA, was significantly reduced. The de-inhibited CDK2 stimulated the phosphorylation of retinoblastoma (Rb) protein and facilitated the G1/S transition and growth rate of the cells. The decrease of p27Kip1 protein, the increase of CDK2 activity and Rb phosphorylation, as well as the cell growth and percentage of S phase cells were correlated to the increased amount of cell surface sialyl Lewis X (SLe(x)) antigen in cells with different alpha-1,3-FucT-VII expression. The reduction in p27Kip1 and the difference in its expression among different transfected cells were blocked by the SLe(x) antibody KM93 in a dose-dependent manner, indicating that p27Kip1 expression was influenced by alpha-1,3-FucT-VII and its product SLe(x). The MEK/MAPK signaling pathway was more important than the PI-3K pathway in the regulation of p27Kip1 expression.
Morphological effects in luminescence properties of a representative semiconducting polymer, poly(2-methoxy-5-(2'-ethylhexyloxy)-1,4-phenylenevinylene) (MEH-PPV), has recently attracted much attention. Previous studies indicated that short-term heat treatment of solution-cast MEH-PPV films may result in the formation of mesomorphic order that is responsible for the "red" emission around 640 nm, in contrast to the single-chromophore "yellow" emission near 590 nm from the disordered matrix. On the basis of microscopic and spectroscopic evidence for films cast from freshly prepared and aged solutions, here we show that prolonged storage of MEHyellowPPV solutions at room temperature or lower may result in retardation of the thermally induced mesophase formation in the subsequently cast films. According to small-angle neutron scattering and differential scanning calorimetric observations over aged MEH-PPV/toluene solutions, we propose that the suppressed transformation into mesomorphic order is due to further development of nanocrystalline aggregates that serve as physical cross-links among MEH-PPV chains in the solution state upon long-term storage. These solvent-induced nanocrystalline aggregates, however, do not exhibit new spectroscopic features beyond the suppression of "red" emission at 640 nm from the mesomorphic phase.
Transfection of sense cDNA of N-acetylglucosamyltransferase V (GnTV-S) into human H7721 hepatocarcinoma cells resulted in an increase in the N-acetylglucosaminebeta1,6mannosealpha1,3- branch (GnT-V product) on the N-glycans of epidermal growth factor (EGF) receptor (EGFR), and promotion of its EGF binding and tyrosine autophosphorylation, but showed little effect on the expression of EGFR protein. The phosphorylation at T308, S473 and tyrosine residue(s) and the activity of protein kinase B (Akt/PKB) as well as the phosphorylation of p42/44 mitogen-activated protein kinase (MAPK) and MAPK kinase (MEK) before and after EGF stimulation were concomitantly increased. Conversely, in the antisense GnT-V (GnTV-AS)-transfected H7721 cells, all the results were the reverse of those with GnTV-S-transfected cells. After the cells were treated with 1-deoxymannojirimycin, an inhibitor of N-glycan processing at high mannose, or antibody against the extracellular glycan domain of EGFR, the differences in PKB activity, p42/44 MAPK and MEK phosphorylation among GnTV-S-, GnTV-AS- and mock-transfected cells were significantly attenuated. These findings indicate that the altered expression of GnT-V will change the glycan structure and function of EGFR, which may modify downstream signal transduction.
The aim of this study was to evaluate the serum polychlorinated dibenzo-p-dioxin (PCDD) and dibenzofuran (PCDF) concentration distribution in residents living in the vicinity of an incinerator and its association with annual ambient dioxin exposure predicted by an atmospheric dispersion model. A municipal waste incinerator in Northern Taiwan was chosen for this study. This incinerator had been in operation for 6 years at the time of this study. Using the incinerator site as the center, based on the simulated ambient annual average PCDD/F concentrations. Ninety-five volunteers, all live within a radius of 5 km from the incinerator for at least 5 years, who had no occupational exposure potential, were selected based on the population distribution in each district. The average serum PCDD/F concentration for these subjects living within four zones was about 14 pg I-TEQ/g lipid. The serum distribution levels of people of the four study zones, however, were not consistent with the predicted ambient levels. Results also suggest that ambient exposure might not be the most important contributor to serum concentrations when compared to other exposure sources, such as dietary intake.
Cationic liposomes modified by different Pluronic block copolymers were prepared. The influence of Pluronic on the cellular uptake of antisense oligonucleotides (ODN) based on cationic 3beta[N-(N', N'-dimethylaminoethan)-carbamoyl] cholesterol (DC-Chol) liposomes was studied by flow cytometric analysis. It showed that DC-Chol liposomes containing Pluronic gave 1.7-2.3 times higher capacity of cellular uptake of ODN, despite the diminution of ODN loading efficiency. The level of improvement by Pluronic is related to the hydrophobic propylene oxide (PO) units Pluronic contains as well as the lipophile/hydrophile value of the molecule. This preliminary study indicated that modifying liposomes with another excipient is a useful pharmaceutical technique to improve ODN delivery.
Various determination methods for protein encapsulation efficiency of PLGA microspheres were compared. Acetonitrile is recommended as an extraction solvent.
The purpose of this study was to compare the levels of interleukin-6 (IL-6) and malondialdehyde (MDA) in healthy controls and diabetic patients without coronary heart disease (CHD). Fasting serum IL-6 and MDA were determined in 30 healthy controls and 52 (20 Type 1 and 32 Type 2) diabetic patients without clinical evidence of CHD. MDA was calculated as oxidative stress. The IL-6 concentration was used to evaluate the cytokine function. Results showed that the serum IL-6 and MDA concentrations are significantly higher in Type 2 diabetic patients (p<0.05). In conclusion, we demonstrated that Type 2 diabetic patients are more influenced by oxidative stress than Type 1 diabetic patients and healthy controls, because of the action of cytokine.
OBJECTIVES: This study examined the influence of root canal space and circumferential undercut placement in the dentine wall on the retention of a prefabricated Root Keeper post. METHODS: Twenty-four extracted single-rooted teeth, having narrow root canal spaces, were decoronated, treated endodontically, and then centrally embedded in resin blocks. All canal spaces were prepared with a no. 2 Peeso reamer to an 8mm depth, and half the specimens were successively treated with a no. 3 Peeso to depths of 5 and 8mm for the small canal group (SC) and large canal group (LC), respectively. An L-type keeper post (Aichi Steel Co.) was luted to each canal with resin cement. The assembly was thermocycled 2000 times (4-60 degrees C), and post retention was measured. Afterwards the dislodged post with the intact structure was sandblasted, and the canal was cleaned and slightly undercut using an inverted cone bur. Six treated posts were recemented for both grooved large canal (GLC) and grooved small canal (GSC) groups, and the repaired retentive strengths were measured. RESULTS: Keeper posts cemented in SC (84.26+/-31.85N) showed better (p<0.05) retention than those cemented in LC (41.92+/-22.36N). Interestingly, the repaired strengths of the recemented post increased in both GSC (104.29+/-11.89N) and GLC (96.65+/-6.91N). All posts, except for one in the GLC, failed at the keeper-post joint. CONCLUSIONS: Prefabricated Root Keeper posts had lower retentive strength in roots with a large canal space. Placement of a circumferential undercut in the root canal wall significantly enhanced the retention of the short tapered posts.
Two trials were conducted to study the effects of two Chinese herbal polysaccharides [achyranthan (ACH), a low-molecular-weight polysaccharide, and astragalan (APS), a high-molecular-weight polysaccaride] on the immunity and growth performance of young broilers. Trial 1 was a 28-d growth assay, in which 7-d-old broilers (n = 240) were randomly allotted to one of three dietary treatments, with eight replicate pens per treatment and ten chickens per pen. Dietary treatments included a control corn-soy-fishmeal (Treatment 1), a diet with 200 mg/kg APS (Treatment 2), and a diet with 200 mg/kg ACH (Treatment 3). Blood samples were collected by cardiac puncture on Days 7, 14, 21, and 28 for determination of serum parameters, and chickens were killed on Day 28 to measure immune organ indexes. Trial 2 was an in vitro trial to study the effects of different concentrations of polysaccharides on broiler splenocyte functions. In Trial 1, feeding either APS or ACH had no significant effects on growth performance of broilers relative to the control. However, compared to the control, feeding ACH significantly increased microhemagglutination inhibition (HI) antibody titers, bursa of Fabricius index, serum albumin, serum calcium, and nitric oxide (NO) concentrations at Day 28 (P < or = 0.05). In Trial 2, both polysaccharides showed significant immunostimulating effects. They increased NO and interleukin-2 (IL-2) production of splenocytes and enhanced splenocyte proliferation in a dose-dependent manner (P < 0.05). Those results indicate that the immunostimulating effects of APS are not as pronounced as those of ACH. Achyranthan showed immunostimulating effects in both the growth assay and in vitro studies. Therefore, ACH may be a Chinese herbal polysaccharide that has the potential to be used as a feed additive to improve broilers' immunity.
Lentinan (LEN) is an intensively studied beta-glucan that has been shown to have immunostimulating and antitumor functions. However, it currently is not used in veterinary practice and animal production. This study was conducted to investigate the impacts of LEN on broiler splenocyte proliferation, interleukin-2 (IL-2) production, and to explore its effects on receptor signal transduction by determining signaling molecules, including nitric oxide (NO), cytosolic-free Ca2+, cytosolic cyclic adenosine monophosphate (cAMP), and cyclic guanosine monophosphate (cGMP). The results showed that compared to the control all three measured doses, including 40, 80, and 160 microg/mL LEN, increased splenocyte proliferation and IL-2 production (P < 0.05). Lentinan increased splenocyte NO production and cytosolic-free calcium concentration in a dose-dependent manner (P < 0.001). After incubating splenocytes for 20 min, LEN increased intracellular cAMP and cGMP concentrations at a dose of 80 and 160 microg/mL, respectively. However, after incubating the splenocytes for 60 min, LEN had no effect on cytosolic cAMP and cGMP concentration irrespective of the LEN dosage. Those results indicated that LEN had immunostimulatory effects on splenocytes by increasing splenocyte proliferation and IL-2 production and by activating splenocyte receptor signal transduction.
The expressions of Lewis antigens on H7721 human hepatocarcinoma cells were detected with monoclonal antibodies and flow-cytometry. It was found that H7721 mainly expressed SLex, and a small amount of SDLex, but Lex and SLea was negligible. The monoclonal antibody of SLex (KM93) significantly blocked the adhesion of H7721 cells to human umbilical vein epithelial cells, as well as cell migration and invasion, but the blocking effect of SDLex antibody (FH6) was not statistically significant. The expressions of five subtypes of alpha1,3fucosyltransferases (alpha1,3FucTs), the enzyme responsible for the fucosylation step in Lewis antigen synthesis, were also studied using real-time RT-PCR. The expression of FucT mRNAs were FucT-IV > FucT-III > FucT-VI > or = FucT-VII > FucT-IX. FucT-VI is supposed to be the main enzyme responsible for the synthesis SLex and SDLex. FucT-VII and III may also participate in SLex synthesis. The absence of FucT-IX expression and FucT-III not being the rate-limiting enzyme for SLea synthesis may be the reasons for the negligible expressions of Lex and SLea on the cell surface, respectively.
The expressions of three X series Lewis antigens, including Lewis X (Le(x)), sialyl Lewis X (SLe(x)) and sialyl dimeric Lewis X (SDLe(x)) were studied with immuno-histochemical methods in human non-small cell pulmonary cancer (NSCPC) and primary liver cancer (PLC) with different pathological conditions. The Lewis antigens are mainly expressed on the cell surfaces, medially or slightly in the cytoplasm, but not in the cell nuclei of the cancer tissues. The regions adjacent to the cancer tissues do not express any Lewis antigens. The positive rates of these antigens in NSCPC were within the range of 75% to approximately 86%. There was no apparent difference in positive rates between the cases with different differentiation and the presence or absence of metastasis in peripheral lymph nodes, nor among the three antigens, except that the positive rate of SDLe(x) was lower (about 56%) in the cases with well/medium differentiation and without metastasis. However, the expression-intensities (SI indexes) of all three antigens were significantly higher in the samples of poor differentiation and with metastasis as compared to those with well/medium differentiation and without metastasis. The two sialyl Lewis antigens increased more significantly than non-sialylated Le(x). The expressions of these antigens were also observed in the peripheral lymph nodes with metastasis, but not in those without metastasis. The positive rates of Le(x), SLe(x) and SDLe(x) in human primary liver cancer were 83.3%, 88.9% and 77.8%, respectively. In the cases with cancer cell thrombosis (CCT) in portal vein (an index of metastasis), the expressions of all these three antigens were stronger than those in the cases without CCT. SLe(x) was the most abundant and most highly increased Lewis antigen on the surface of NSCPC and PLC, especially in the cases with poor differentiation and metastasis. In the study of the enzymatic basis of the increased Lewis antigens in PLC by using Northern blot, it was found that the level of alpha1,3 FucT-III/VI mRNA in PLC tissues was much higher than that in the adjacent regions, and more significantly higher in the cancer tissues from patients with CCT in portal vein. In contrast, the expression of alpha1,3 FucT-VII was rather low in cancer tissues and not different from the adjacent regions in spite of the presence or absence of CCT. These results reveal that the SLe(x) in PLC is mainly synthesized by alpha1,3 FucT-III/VI (especially VI) and is the most important Lewis antigen involved in the metastasis of PLC.
Both bone morphogenetic proteins (BMPs) and glial cell line-derived neurotrophic factor (GDNF) reduce ischemia-induced cerebral injury in rats. Intracerebral transplantation of fetal kidney tissue, which normally expresses BMPs and GDNF during development, reduces ischemic injury in cerebral cortex. In this study, we tested the hypothesis that BMP is involved in this neuroprotective response. Fetal kidney tissue was cut into small pieces and transplanted into cortical areas adjacent to the right middle cerebral artery (MCA) in adult rats. In situ hybridization of brain indicated that these fetal kidney transplants contained high levels of BMP-7 mRNA three days after grafting. Immunohistochemical analysis of grafted brain showed co-localization of BMP-7 and PAX-2 immunoreactivity in the graft, suggesting that these transplants contained BMP protein. Some animals were grafted with fetal kidney tissue after intraventricular administration (ICV) of the BMP antagonist noggin (1 micro g) or after vehicle, followed by MCA ligation for 60 min. Animals receiving fetal kidney tissue transplantation developed significantly less body asymmetry, as compared to stroke animals that either did not receive transplantation or received fetal kidney grafts and noggin pretreatment. Analysis of these brains after triphenyltetrazolium chloride staining showed that fetal kidney tissue transplantation reduced the volume of infarction in the cerebral cortex. Noggin pretreatment reduced the protection induced by fetal kidney grafting, although noggin itself did not cause increase in cerebral infarction. Eight hours after ischemia, brain homogenates were obtained from grafted and control animals to assay caspase-3 enzymatic activity. This analysis demonstrated that fetal kidney grafts significantly reduced ischemia-induced caspase-3 activity. Reduction of caspase-3 activity could also be antagonized by noggin pretreatment. In conclusion, our data suggest that fetal kidney transplantation reduces ischemia/reperfusion-induced cortical infarction and behavioral deficits in adult rats, which are, at least partially, mediated through the effect of BMPs from the transplants.
BACKGROUND: Hepatitis B virus (HBV) infection is hyperendemic in Taiwan. Before universal HBV immunization was started in Taiwan in 1984, the carrier rate for hepatitis B surface antigen (HBsAg) was 15% to 20% in the general population. OBJECTIVE: To quantify the population impact of a mass vaccination program for HBV 15 years after its implementation. DESIGN: Descriptive analysis of serologic markers of HBV in healthy children and adolescents. SETTING: Chung-Cheng District, Taipei City, Taiwan, in 1999. PARTICIPANTS: 1357 persons younger than 15 years of age, who were born after the implementation of universal HBV vaccination, and 559 persons 15 to 20 years of age, who were born before the program began. MEASUREMENTS: Repeated serologic surveys similar to those done before and 5 and 10 years after the national vaccination program was implemented. All participants were tested for serum HBsAg, its antibody (anti-HBs), and hepatitis B core antibody (anti-HBc). RESULTS: During the 15 years since the vaccination program was implemented, the prevalence of HBsAg among persons younger than 15 years of age decreased from 9.8% in 1984 to 0.7% in 1999; among persons 15 to 20 years of age, the 1999 prevalence of HBsAg was 7% (P < 0.001). Hepatitis B core antibody seropositivity, which represents HBV infection, was found in 2.9% of persons younger than 15 years of age and in 20.6% of persons 15 to 20 years of age (P < 0.001); in the same age groups, the rate of anti-HBs seropositivity was 75.8% and 70.7%, respectively (P = 0.02). CONCLUSIONS: Universal vaccination significantly decreased the HBV carrier rate and infection rate among children and adolescents born since the program began. By decreasing the carrier pool, continuation of the national HBV immunization program should prevent HBV infection in the children of Taiwan, and, subsequently, adults as well.
The expressions of Lewis (Le) antigens, alpha-1,3/1,4 fucosyltransferases (alpha-1,3/1,4 FuTs), and metastatic potential after the treatment of 2 differentiation inducers, all- trans retinoic acid (ATRA), 8-bromo-cyclic 3',5'adenosine monophosphate (8-Br-cAMP); and 2 proliferation inducers, epidermal growth factor (EGF) and phobol-12-myristate-13-acetate (PMA), on 7721 human hepatocarcinoma cell line were studied. Cell adhesion to human umbilical vein endothelial cells (HUVEC), cell migration through transwell and invasion through matrigel were selected as the indexes of metastatic potential-related phenotypes. Using fluorescence-labelled antibodies and flow-cytometric analysis, it was found that 7721 cells mainly expressed sialyl Lewis X (SLe(x)) and a less amount of sialyl dimeric Lewis X (SDLe(x)) antigens on the cell surface. Their expressions were down-regulated by ATRA, and up-regulated by EGF. SLe(x)antigen was also decreased and increased by the treatment of 8-Br-cAMP and PMA respectively. With Northern blot to detect the mRNAs of alpha-1,3/1,4 FuTs, the main enzymatic basis for the change in SLe(x)expression was found to be the alteration of the expression of alpha-1,3 FuT-VII. It was evidenced by the observations that alpha-1,3 FuT-VII was the main alpha-1,3/1,4 FuT in 7721 cells, while alpha-1,3/1,4 FuT-III and alpha-1,3 FuT-VI were expressed rather low. The changes in the expressions of SLe(x)antigen and alpha-1,3 FuT-VII resulted in the altered cell adhesion to tumour necrosis factor-alpha stimulated HUVEC, since only the monoclonal antibody of the SLe(x), but not other monoclonal antibodies blocked the adhesion of 7721 cells to HUVEC. The migration and invasion of 7721 cells were also reduced by the treatment of ATRA or 8-Br-cAMP, and elevated by EGF or PMA. The above findings indicate that the metastatic potential of 7721 cells is suppressed by differentiation-inducers and promoted by proliferation-inducers.
This study was undertaken to examine the seasonal variations of domestic Der p 1, Der p 2, and endotoxin on mattress and airborne fungal concentrations in homes of asthmatic and nonasthmatic children in southern Taiwan, where temperature and relative humidity are usually high throughout the year. A group of asthmatic children (10-12 years old) were selected randomly based on a citywide questionnaire survey. The nonasthmatic children were chosen to be in the comparison group by matching in age, gender, and proximity of residence. Environmental sampling of domestic microbes was conducted once a month for a year. Twelve calendar months were grouped into spring, summer, fall, and winter according to weather data (mainly average temperature and humidity) from the Central Weather Bureau. Dust samples from a child's mattress and airborne samples from a child's bedroom were collected and analyzed for allergens of Der p 1 and Der p 2, endotoxin, and fungi respectively. Results show that about 65% of children's mattresses in our region have Der p 1 levels greater than 2 microg/g. It is also apparent that most airborne fungal concentrations found in homes of either asthmatic or nonasthmatic children are higher than the recommended levels of concern. The predominant genera are Cladosporium, Aspergillus, Penicillium, Alternaria, and yeast. In addition, seasonal effects seem to be a critical factor for the concentrations and distributions of domestic endotoxin in these study homes. The implication of long-term exposure to these high levels of environmental microbes and how their effects vary with seasons remain to be further characterized.